Is there a common binding center in the ADP, ATP carrier for substrate and inhibitors?

Atractyloside and bongkrekic acid sites in the mitochondrial ADP/ATP carrier protein

“…In brief, Klingenberg et al [7,8] and our group [4,5] agree on the two different extreme conformations assumed by the ADP/ATP carrier protein (ATR conformation or c-state, and BA conformation or m-state). The identity of the ATR and BA sites remains, however, a matter of debate (two pre-existing sites capable of interacting and changing their conformation [4,5] or same site with two possible conformations [7,8]). Because the ADP/ATP carrier is unique among transport systems by its ability to be probed in two conformations (ATR and BA conformations) that probably correspond to two frozen states of the transport process, full elucidation of the topology of the ATR and BA sites is clearly desirable for better understanding of the functioning of this carrier.…”

“…This result was explained in [8] by an ADP-induced shift from the c-state (with high affinity for ATR) to the m-state (which is unable to bind ATR); it was further postulated [8] that SH-groups buried in the c-state are unmasked in the m-state, and can therefore be alkylated by NEM, resulting in a …”

“…The c-state would be recognized specifically by ATR, and the m-state by BA. In [8] it was admitted that beside the connnon binding area, called also binding center, molecules of ATR and BA should occupy additional areas, although no specific function was ascribed for these additional areas. In brief, Klingenberg et al [7,8] and our group [4,5] agree on the two different extreme conformations assumed by the ADP/ATP carrier protein (ATR conformation or c-state, and BA conformation or m-state).…”

“…In [8] it was admitted that beside the connnon binding area, called also binding center, molecules of ATR and BA should occupy additional areas, although no specific function was ascribed for these additional areas. In brief, Klingenberg et al [7,8] and our group [4,5] agree on the two different extreme conformations assumed by the ADP/ATP carrier protein (ATR conformation or c-state, and BA conformation or m-state). The identity of the ATR and BA sites remains, however, a matter of debate (two pre-existing sites capable of interacting and changing their conformation [4,5] or same site with two possible conformations [7,8]).…”

“…Because the ADP/ATP carrier is unique among transport systems by its ability to be probed in two conformations (ATR and BA conformations) that probably correspond to two frozen states of the transport process, full elucidation of the topology of the ATR and BA sites is clearly desirable for better understanding of the functioning of this carrier. Along this line, selective chemical modifications of strategic amino acids in the ADP/ATP carrier have already provided interesting data [4,5,8]. The penetrant reagents used so tar and their main targets include NEM (SH groups) [91, HNB (tryptophanyl residues) [10], phenylglyoxal and butanedione (arginyl residues [ 11,12]).…”